POS1384 NON-INVASIVE IN VIVO METABOLIC PROFILING OF INFLAMMATION IN JOINTS AND ENTHESES BY OPTOACOUSTIC IMAGING
Authors: K. Tascilar, F. Fagni, A. Kleyer, S. Bayat, R. Heidemann, F. Steiger, G. Krönke, D. Bohr, A. Ramming, F. Hartmann, D. Klett, A. Federle, A. Regensburger, A. L. Wagner, F. Knieling, M. F. Neurath, G. Schett, M. Waldner, D. Simon
Journal: Annals of the Rheumatic Diseases (2022)

Background An in-depth metabolic characterization of joints and entheses at the tissue level can help in the early diagnosis and treatment selection for patients with inflammatory arthritis [1]. However, current knowledge about the metabolic profiles of synovitis and enthesitis is limited. Multispectral optoacoustic tomography (MSOT), a novel metabolic imaging technology, could be used to undertake metabolic profiling of joints and entheses non-invasively using near-infrared multispectral laser to stimulate tissues and detect the emitted acoustic energy, enabling quantification of tissue components in vivo based on differential absorbance at multiple wavelengths [2, 3]. Objectives To explore the metabolic characteristics of arthritis and enthesitis using MSOT. Methods We performed a cross sectional study on healthy controls (HC) and patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) (Table 1). Participants underwent clinical, ultrasound (US), and MSOT examination of metacarpophalangeal joints, wrists, entheses of lateral epicondyles, patellar, quadriceps and Achilles tendons. MSOT-derived hemoglobin, oxygen saturation, collagen and lipid levels were measured. We calculated scaled mean differences (SMD) between affected and unaffected joints and entheses as defined by clinical examination or US using linear mixed effects models. Table 1. Baseline characteristics. Overall Healthy PsA RA N 87 36 34 17 Age, mean (SD) 47.0 (15.7) 34.7 (12.0) 52.4 (11.5) 62.5 (9.1) Sex, n (%) Female 48 (55.2) 18 (50.0) 17 (50.0) 13 (76.5) Male 39 (44.8) 18 (50.0) 17 (50.0) 4 (23.5) Tender joints, median (IQR) 0 (0-2) 0 (0-0) 1 (0-5) 2 (1-6) Swollen joints, median (IQR) 0 (0-1) 0 (0-0) 0 (0-2) 2 (1-6) Tender entheses, median (IQR) 0 (0-2) 0 (0-0) 1 (0-3) 0 (0-0) csDMARD, n (%) 22 (25.3) - 13 (38.3) 9 (53.0) b-tsDMARD, n (%) 31 (35.6) - 20 (58.8) 11 (64.7) SD, standard deviation; IQR, interquartile range; csDMARD, conventional synthetic disease modifying anti-rheumatic drug; b-tsDMARD, biologic or targeted synthetic disease modifying anti-rheumatic drug. Results We obtained 1535 MSOT and 982 US scans from 87 participants (36 HC, 34 PsA, 17 RA). Entheseal tenderness was not associated with metabolic changes, whereas US enthesitis was associated with increased total hemoglobin, oxygen saturation and collagen content. In contrast, clinical and US arthritis showed increased hemoglobin levels but reduced oxygen saturation and reduced collagen content. Synovial hypertrophy was associated with increased lipid content in the joints (Figure 1). Figure 1. Scaled differences and 95% confidence intervals of MSOT-measured metabolite values by clinical and ultrasonographic findings of enthesitis (A-C) and arthritis (D-F). Two differences are plotted for each metabolite indicating two multispectral processing algorithms used for estimation. P values were adjusted for multiple testing using a false discovery rate of 5%. NS, not significant. sO 2 , oxygen saturation. Conclusion MSOT allows a non-invasive characterization of metabolic changes in arthritis and enthesitis. These findings can be interpreted as a reflection of increased synovial cellularity, collagen degradation, and metabolic demand in synovitis, and of an increased tissue apposition and vascularization in enthesitis. Our results suggest that synovitis and enthesitis do not only differ at the clinical and anatomical-functional level, but also exhibit divergent metabolic changes. References [1]Falconer J, et. al. Arthritis Rheumatol. 2018;70(7):984-99. [2]Regensburger AP, et. al. Biomedicines. 2021;9(5). [3]Regensburger AP, et al. Nature Medicine. 2019;25(12):1905-15. Conflict of Interest AR., FK, MW are co-inventors, together with iThera Medical GmbH, Germany on an EU patent application (no. EP 19 163 304.9) relating to a device and a method for analysis of optoacoustic data, an optoacoustic system and a computer program. All other authors declare no conflict of interest. Acknowledgements We thank Ms. Nairouz Al Ahmad, assistant medical technician (Department of Internal Medicine 3), for her assistance in conducting the study and Dr. Yi Qiu, PhD (iThera Medical GmbH) for her assistance in data analysis and interpretation. Disclosure of Interests None declared